Factors that contribute to the immmunogenicity of therapeutic recombinant human proteins

Ilya Mukovozov; Thomas Sabljic; Gonzalo Hortelano; Frederick A. Ofosu

doi:10.1160/TH07-11-0654

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2008; 99(05): 874-882
DOI: 10.1160/TH07-11-0654

Theme Issue Article

Schattauer GmbH

Factors that contribute to the immmunogenicity of therapeutic recombinant human proteins

Ilya Mukovozov

¹Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada

,

Thomas Sabljic

¹Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada

,

Gonzalo Hortelano

¹Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada

³School of Bioengineering, McMaster University, Hamilton, Ontario, Canada

,

Frederick A. Ofosu

²Canadian Blood Services and Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada

› Institutsangaben

Abstract

Summary

Use of recombinant human proteins has revolutionized medicine by providing over 200 highly purified hormones and proteins that effectively treat many inherited and acquired peptide hormone and protein deficiencies. With the exception of therapeutic monoclonal antibodies, these biological medicines are synthesized by cultured cells using DNA sequences that would yield proteins with identical amino acid sequences as endogenous human proteins. Therefore, there was the broad expectation that recombinant human biological medicines would be non-immunogenic in patients capable of synthesizing even sub-optimal levels of these therapeutic proteins to which they are innately tolerant. However, the widespread clinical use of recombinant human proteins has demonstrated that nearly all of them are immunogenic. This observation suggests that factors additional to differences in amino acid sequences of endogenous and biotherapeutic proteins contribute to the immunogenicity of therapeutic proteins. The main aim of this review is to summarize some of the factors that are known to contribute to the immunogenicity of recombinant therapeutic proteins.

Keywords

Therapeutic proteins - immunogenicity - recombinant human proteins

Volltext

Referenzen

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